Article ; Online: RNA-Based Homologous Recombination Deficiency Signature Detects Homologous Recombination Deficiency-RNA+ Patients With and Without Homologous Recombination Repair Gene Pathogenic Alterations in Men With Prostate Cancer.
JCO precision oncology
2023 Volume 7, Page(s) e2300378
Abstract: Purpose: Homologous recombination deficiency (HRD) is a well-described phenotype of some prostate cancers; however, current biomarkers for HRD are imperfect and rely on detection of single gene alterations in the homologous recombination repair (HRR) ... ...
Abstract | Purpose: Homologous recombination deficiency (HRD) is a well-described phenotype of some prostate cancers; however, current biomarkers for HRD are imperfect and rely on detection of single gene alterations in the homologous recombination repair (HRR) pathway, which may not capture the complexity of HRD biology. RNA signature-based methods of HRD identification present a potentially dynamic assessment of the HRD phenotype; however, its relationship with HRR gene alterations is not well characterized in prostate cancer. Methods: A HRD assay on the basis of an RNA signature associated with biallelic Results: In this cohort, of the 126 (13%) patients found to be HRD+ by RNA signature (HRD-RNA+), 100 (79%) had no coexisting HRR gene alteration. Among samples with biallelic Conclusion: Use of an RNA-based HRD signature significantly expands the fraction of patients with prostate cancer who may derive benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) compared with using HRR gene mutations alone. Further studies are needed to evaluate functional HRD significance and inform future usage as a predictive biomarker for PARPi selection. |
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MeSH term(s) | Male ; Humans ; BRCA1 Protein/genetics ; Recombinational DNA Repair/genetics ; Homologous Recombination/genetics ; Retrospective Studies ; BRCA2 Protein/genetics ; Prostatic Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors |
Chemical Substances | BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein ; Poly(ADP-ribose) Polymerase Inhibitors |
Language | English |
Publishing date | 2023-06-14 |
Publishing country | United States |
Document type | Journal Article |
ISSN | 2473-4284 |
ISSN (online) | 2473-4284 |
DOI | 10.1200/PO.23.00378 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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